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Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study

Phase 2
Recruiting
Conditions
Epilepsy
Tuberous Sclerosis Complex
Interventions
Drug: Sirolimus
Drug: Placebo
Registration Number
NCT05104983
Lead Sponsor
Darcy Krueger
Brief Summary

This trial is a Phase II randomized, double-blind, placebo controlled multi-site study to evaluate the safety and efficacy of early sirolimus to prevent or delay seizure onset in TSC infants.

This study is supported by research funding from the Office of Orphan Products Division (OOPD) of the US Food and Drug Administration (FDA).

Detailed Description

Tuberous Sclerosis Complex (TSC) is caused by genetic mutation in TSC1 or TSC2, resulting in dysregulation of the mechanistic target of rapamycin (mTOR) signaling pathway. Age at time of seizure onset in TSC infants has been linked to long-term neurodevelopmental outcome in this high-risk population. Sirolimus is an mTOR inhibitor used to treat many of the symptoms of TSC, including epilepsy. This will be the first study to truly evaluate a targeted, disease-modifying drug therapy for preventing or delaying seizure onset in TSC using a rational, mechanism-based therapeutic approach.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
64
Inclusion Criteria
  1. 0-6 months of age at the time of enrollment (subject must be <7 months of chronological age at time of randomization and treatment initiation). Corrected age must be at least 39 weeks (calculated by subtracting the number of weeks born before 40 weeks gestation from the chronological age).
  2. Has a confirmed diagnosis of TSC based on established clinical or genetic criteria
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Exclusion Criteria
  1. Prior history of seizures (clinical or electrographic) at the time of enrollment or identified on baseline EEG.
  2. Has been treated in the past or is currently being treated at the time of enrollment with conventional anticonvulsant medications (AEDs), systemic (oral) mTOR inhibitors (such as rapamycin, sirolimus, or everolimus), ketogenic-related special diet, or another anti-seizure therapeutic agent, device, or procedure.
  3. Has taken any other investigational drug as part of another research study, within 30 days prior to the baseline screening visit.
  4. Has a significant illness or active infection at the time of the baseline screening visit
  5. Has a history of significant prematurity, defined as gestational age <30 weeks at the time of delivery, or other significant medical complications at birth or during the neonatal period that other than TSC would convey additional risk of seizures or neurodevelopmental delay (i.e. HIE, severe neonatal infection, major surgery, prolonged ventilatory or other life-saving supportive care or procedures).
  6. Abnormal laboratory values at baseline (i.e., renal function, liver function, or bone marrow production) that are in the opinion of the investigator clinically significant and may jeopardize the safety of the study subject.
  7. Prior, planned or anticipated neurosurgery within 3 months of the baseline visit
  8. Has a TSC-associated condition for which mTOR treatment is clinically indicated (i.e. SEGA or AML).
  9. Subjects who are, in the opinion of the investigator, unable to comply with the requirements of the study.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SirolimusSirolimusSirolimus
PlaceboPlaceboPlacebo
Primary Outcome Measures
NameTimeMethod
Efficacy -- time to seizure onset12 months of age

Time to seizure onset, comparing sirolimus with placebo

Safety -- adverse events12 months of age

Percentage of subjects reporting severe (CTCAE v5.0 grade \>= 3) adverse event (AE) or serious adverse event (SAE), comparing sirolimus with placebo.

Secondary Outcome Measures
NameTimeMethod
MRI Biomarkers12 and 24 months of age

MRI measures of neuronal connectivity, comparing sirolimus with placebo.

Neurodevelopmental Outcomes12 and 24 months of age

Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.

Sirolimus Precision Dosing12 months of age

Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC

Quality of Life Outcomes12 and 24 months of age

Patient and caregiver quality of life, comparing sirolimus with placebo.

EEG Biomarkers12 and 24 months of age

EEG measures of neuronal connectivity, comparing sirolimus with placebo.

Trial Locations

Locations (9)

University of California at Los Angeles

🇺🇸

Los Angeles, California, United States

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

University of Texas HSC at Houston

🇺🇸

Houston, Texas, United States

Stanford University

🇺🇸

Palo Alto, California, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Washington University -- St. Louis

🇺🇸

Saint Louis, Missouri, United States

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